Mississippi's 1st congressional district is in the northeast corner of the state. It includes much of the northern portion of the state including Columbus, Oxford, Southaven, and Tupelo. One of the state's major universities, the University of Mississippi (Ole Miss), is located within the district at Oxford.

From statehood to the election of 1846, Mississippi elected representatives at-large statewide on a general ticket.

The congressional seat has been held by Republican Trent Kelly who won a June, 2015 special election to fill the vacant seat previously held by Republican Alan Nunnelee who died February 6, 2015. In the November 2010 election, Nunnelee had defeated Democratic incumbent Travis Childers, Constitutionalist Gail Giaramita, Independent Conservative Party candidate Wally Pang of Batesville, Libertarian Harold Taylor, and Reformist Barbara Dale Washer.